rs41284066

Variant names:

• chr10-80280367-G-A
• rs41284066
• NM_000429.3:c.406-51C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-80280367-G-A
• chr10-80280367-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000429.3(MAT1A):​c.406-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 1,607,964 control chromosomes in the GnomAD database, including 2,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (211 hom., cov: 31)
  • Exomes 𝑓: 0.048 (1985 hom.)
• Consequence: MAT1A NM_000429.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.347
• Publications: 3 publications found

Genes affected

MAT1A (HGNC:6903): (methionine adenosyltransferase 1A) This gene catalyzes a two-step reaction that involves the transfer of the adenosyl moiety of ATP to methionine to form S-adenosylmethionine and tripolyphosphate, which is subsequently cleaved to PPi and Pi. S-adenosylmethionine is the source of methyl groups for most biological methylations. The encoded protein is found as a homotetramer (MAT I) or a homodimer (MAT III) whereas a third form, MAT II (gamma), is encoded by the MAT2A gene. Mutations in this gene are associated with methionine adenosyltransferase deficiency. [provided by RefSeq, Jul 2008]

MAT1A Gene-Disease associations (from GenCC):

• methionine adenosyltransferase deficiency

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-80280367-G-A is Benign according to our data. Variant chr10-80280367-G-A is described in ClinVar as Benign. ClinVar VariationId is 1178402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT1A	NM_000429.3	c.406-51C>T		intron_variant	Intron 4 of 8	ENST00000372213.8	NP_000420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT1A	ENST00000372213.8	c.406-51C>T		intron_variant	Intron 4 of 8	1	NM_000429.3	ENSP00000361287.3
MAT1A	ENST00000455001.1	c.217-51C>T		intron_variant	Intron 3 of 4	5		ENSP00000414961.1

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8211 AN: 151968 Hom.: 210 Cov.: 31

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0399

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0399

Gnomad FIN AF: 0.0613

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.0412

GnomAD2 exomes AF: 0.0475 AC: 11728 AN: 246698 AF XY: 0.0488

Gnomad AFR exome AF: 0.0594

Gnomad AMR exome AF: 0.0233

Gnomad ASJ exome AF: 0.0974

Gnomad EAS exome AF: 0.000547

Gnomad FIN exome AF: 0.0611

Gnomad NFE exome AF: 0.0545

Gnomad OTH exome AF: 0.0502

GnomAD4 exome AF: 0.0482 AC: 70220 AN: 1455878 Hom.: 1985 Cov.: 35 AF XY: 0.0487 AC XY: 35260 AN XY: 724444

African (AFR) AF: 0.0622 AC: 2077 AN: 33392

American (AMR) AF: 0.0244 AC: 1091 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 2534 AN: 26092

East Asian (EAS) AF: 0.000353 AC: 14 AN: 39660

South Asian (SAS) AF: 0.0449 AC: 3866 AN: 86116

European-Finnish (FIN) AF: 0.0593 AC: 3010 AN: 50786

Middle Eastern (MID) AF: 0.0531 AC: 295 AN: 5552

European-Non Finnish (NFE) AF: 0.0490 AC: 54409 AN: 1109438

Other (OTH) AF: 0.0486 AC: 2924 AN: 60218

GnomAD4 genome AF: 0.0539 AC: 8205 AN: 152086 Hom.: 211 Cov.: 31 AF XY: 0.0541 AC XY: 4022 AN XY: 74358

African (AFR) AF: 0.0611 AC: 2534 AN: 41488

American (AMR) AF: 0.0398 AC: 608 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0896 AC: 311 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5164

South Asian (SAS) AF: 0.0389 AC: 187 AN: 4810

European-Finnish (FIN) AF: 0.0613 AC: 650 AN: 10596

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0552 AC: 3753 AN: 67962

Other (OTH) AF: 0.0403 AC: 85 AN: 2108

Alfa AF: 0.0663 Hom.: 67

Bravo AF: 0.0508

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.64
PhyloP100		-0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41284066; hg19: chr10-82040123;